Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system

Smith, Barbara L.; Gadd, Michele A.; Lanahan, Conor R.; Rai, Upahvan; Tang, Rong; Rice-Stitt, Travis; Merrill, Andrea; Strasfeld, David B.; Ferrer, Jorge; Brachtel, Elena F.; Specht, Michelle C.

doi:10.1007/s10549-018-4845-4

Cited by 73 publications

(89 citation statements)

References 25 publications

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“…Use of this system for breast cancer lumpectomies has been previously described. 21 The imaging probe has a 2.6-cmdiameter circular field of view and an outer diameter of 3.1 cm with an angled neck that facilitates contact with lateral and anterior cavity walls.…”

Section: Methodsmentioning

confidence: 99%

“…LUM015 fluorescent signal was correlated with histopathology on hematoxylin and eosin stained slides. 22 The study started with a tumor detection algorithm established from ex vivo imaging data from our Phase 1 19 and pilot 21 studies. This was used to (1) establish the tumor detection threshold for each patient during their intraoperative imaging session and (2) guide the surgeon in excising additional tissue.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported the first human in vivo use of the LUM Imaging System during breast cancer lumpectomy surgery. 21 Both invasive tumor and ductal carcinoma in situ (DCIS) were rapidly distinguished from normal tissue with high sensitivity and good specificity. We now describe results of a feasibility study of the LUM Imaging System for intraoperative detection of residual tumor during breast cancer lumpectomy surgery.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery

et al. 2020

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Background. Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. Methods. Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with realtime predictive results displayed on a monitor intraoperatively, and later correlated with histopathology. Results. In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter The original version of this article was revised due to a retrospective Open Access order.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery

et al. 2020

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“…Cathepsin-targeting probes have been investigated for use in tumor detection and fluorescence-guided tumor surgical resection in preclinical studies or early-phase clinical trials [9,10,16,[38][39][40][41][42][43][44]. These probes are based on fluorescently labeled inhibitors or substrates.…”

Section: Discussionmentioning

confidence: 99%

Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model

et al. 2020

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Purpose The reoperation rate for breast-conserving surgery is as high as 15–30% due to residual tumor in the surgical cavity after surgery. In vivo tumor-targeted optical molecular imaging may serve as a red-flag technique to improve intraoperative surgical margin assessment and to reduce reoperation rates. Cysteine cathepsins are overexpressed in most solid tumor types, including breast cancer. We developed a cathepsin-targeted, quenched fluorescent activity-based probe, VGT-309, and evaluated whether it could be used for tumor detection and image-guided surgery in syngeneic tumor-bearing mice. Methods Binding specificity of the developed probe was evaluated in vitro. Next, fluorescent imaging in BALB/c mice bearing a murine breast tumor was performed at different time points after VGT-309 administration. Biodistribution of VGT-309 after 24 h in tumor-bearing mice was compared to control mice. Image-guided surgery was performed at multiple time points tumors with different clinical fluorescent camera systems and followed by ex vivo analysis. Results The probe was specifically activated by cathepsins X, B/L, and S. Fluorescent imaging revealed an increased tumor-to-background contrast over time up to 15.1 24 h post probe injection. In addition, VGT-309 delineated tumor tissue during image-guided surgery with different optical fluorescent imaging camera systems. Conclusion These results indicate that optical fluorescent molecular imaging using the cathepsin-targeted probe, VGT-309, may improve intraoperative tumor detection, which could translate to more complete tumor resection when coupled with commercially available surgical tools and techniques.

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“…However, the frozen section cannot be completely omitted in breast conserving surgery to evaluate the status of surgical margins. Several studies reported the results of fluorescence-guided margin assessment in breast conserving surgery to compensate for this disadvantage [25][26][27][28]. However, a specific device and agent are necessary to conduct such studies.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of intraoperative ultrasound for margin assessment in breast conserving surgery

Lee

Park

Kim

et al. 2020

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Background: Surgical margin negativity is highly related to local recurrence of breast cancer. The authors performed this study to evaluate if specimen mammography or ultrasonography can replace the frozen section procedure for surgical margins. Methods: One-hundred fifty five patients with breast cancer were included in this study. After the surgery, the frozen biopsies were assessed in more than three different directions, and all specimens were analyzed with mammography and ultrasonography. The clinicopathologic characteristics of the patients were assessed, and closest tumor margin–resection margin distance (TM–RM distance) to the tumor was compared among specimen mammography, ultrasonography, and pathology. Results: On comparing initial cases of positive and negative margins, the mean closest TM–RM distance in specimen ultrasonography and final pathologic reports was statistically different between both groups (DCIS: p < 0.001, p = 0.006; IDC: p = 0.042, p = 0.022). Conclusion: When the closest TM–RM distance is less than 1.8 mm in specimen ultrasonography, the frozen section cannot be waived because of high risk of margin positivity. However, if the closest TM–RM distance is >4 mm in specimen ultrasonography, the frozen section can be omitted carefully because of the very low risk of margin positivity.

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Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system

Abstract: The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

Cited by 73 publications

References 25 publications

Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery

Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery

Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model

Clinical efficacy of intraoperative ultrasound for margin assessment in breast conserving surgery

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